Selenium (Se) is an essential trace element that has several functions in cellular processes related to cancer prevention. While the cancericidal effect of Se has been reported in liver cancer, the mechanism has not been clarified. MiR-29a has widely been reported as a tumor suppressor; however, it also acts as a carcinogenic agent by increasing cell invasion in human epithelial cancer cells and hepatoma cells. In a previous study, we found that miR-29a-3p is a Se-sensitive miRNA. However, its effect in the chicken hepatocellular carcinoma cell line (LMH) is still unknown. In the present study, we found that the expression of miR-29a-3p in LMH cells was decreased by Se supplementation and increased under Se-deficient conditions. Flow cytometry and CCK-8 results suggested that Se decreased LMH cell proliferation induced by miR-29a-3p overexpression. Transwell and gap-closure assays implied that Se mediated LMH cell invasion and migration by downregulating miR-29a-3p. Quantitative real-time polymerase chain reaction and Western blotting results suggested that Se mitigated miR-29a-3p overexpression-induced LMH cell proliferation by downregulating CDK2, cyclin-D1, CDK6, and cyclin-E1. We further demonstrated that collagen type IV alpha 2 (COL4A2) is a target gene of miR-29a-3p. COL4A2 activates the RhoA/ROCK pathway to promote LMH cell invasion and migration. In conclusion, Se mediated miR-29a-3p overexpression induced LMH cell invasion and migration by targeting COL4A2 to inactivate the RhoA/ROCK pathway.

中文翻译：

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硒介导的gga-miR-29a-3p通过靶向COL4A2来调节LMH细胞的增殖，侵袭和迁移。

硒（Se）是必需的微量元素，在与癌症预防相关的细胞过程中具有多种功能。尽管已经报道了硒在肝癌中的致癌作用，但其机理尚未阐明。MiR-29a已被广泛报道为一种肿瘤抑制因子。然而，它也通过增加人类上皮癌细胞和肝癌细胞的细胞侵袭而充当致癌剂。在先前的研究中，我们发现miR-29a-3p是Se敏感的miRNA。但是，其在鸡肝细胞癌细胞系（LMH）中的作用仍然未知。在本研究中，我们发现，补充硒会降低LMH细胞中miR-29a-3p的表达，而在缺硒条件下会增加。流式细胞仪和CCK-8结果表明，硒减少了miR-29a-3p过表达诱导的LMH细胞增殖。Transwell和间隙封闭分析表明，Se通过下调miR-29a-3p介导了LMH细胞的侵袭和迁移。实时定量聚合酶链反应和蛋白质印迹结果表明，Se通过下调CDK2，cyclin-D1，CDK6和cyclin-E1减轻了miR-29a-3p过表达诱导的LMH细胞增殖。我们进一步证明了IV型胶原蛋白α2（COL4A2）是miR-29a-3p的靶基因。COL4A2激活RhoA / ROCK途径，促进LMH细胞的侵袭和迁移。总之，Se介导的miR-29a-3p过表达通过靶向COL4A2使RhoA / ROCK通路失活，诱导LMH细胞侵袭和迁移。实时定量聚合酶链反应和蛋白质印迹结果表明，Se通过下调CDK2，cyclin-D1，CDK6和cyclin-E1减轻了miR-29a-3p过表达诱导的LMH细胞增殖。我们进一步证明了IV型胶原蛋白alpha 2（COL4A2）是miR-29a-3p的靶基因。COL4A2激活RhoA / ROCK途径，促进LMH细胞的侵袭和迁移。总之，Se介导的miR-29a-3p过表达通过靶向COL4A2使RhoA / ROCK通路失活，诱导LMH细胞侵袭和迁移。实时定量聚合酶链反应和蛋白质印迹结果表明，Se通过下调CDK2，cyclin-D1，CDK6和cyclin-E1减轻了miR-29a-3p过表达诱导的LMH细胞增殖。我们进一步证明了IV型胶原蛋白alpha 2（COL4A2）是miR-29a-3p的靶基因。COL4A2激活RhoA / ROCK途径，促进LMH细胞的侵袭和迁移。总之，Se介导的miR-29a-3p过表达通过靶向COL4A2使RhoA / ROCK通路失活，诱导LMH细胞侵袭和迁移。COL4A2激活RhoA / ROCK途径，促进LMH细胞的侵袭和迁移。总之，Se介导的miR-29a-3p过表达通过靶向COL4A2使RhoA / ROCK通路失活，诱导LMH细胞侵袭和迁移。COL4A2激活RhoA / ROCK途径，促进LMH细胞的侵袭和迁移。总之，Se介导的miR-29a-3p过表达通过靶向COL4A2使RhoA / ROCK通路失活，诱导LMH细胞侵袭和迁移。